Process for the manufacture of aromatic 1,3-diketones

ABSTRACT

Aromatic 1,3-diketones are produced by reacting aromatic compounds with acetoacetyl fluoride optionally substituted in γ-position by fluorine, chlorine and/or bromine, in hydrofluoric acid of at least 90% strength at a temperature of from about -40 to +50°C. The products obtained are important starting products and intermediates for the manufacture of dyestuffs, plastics and pharmaceuticals. Furthermore they can be used for the formation of metal complexes and metal extracting agents, solution intermediaries and solvents.

This invention relates to a process for the manufacture of aromatic1,3-diketones.

It is known to react benzene and benzene derivatives, for exampletoluene, o-, m-, and p-xylene, chlorobenzene and diphenyl ether, withdiketene in the presence of 2 mols of aluminum chloride at a temperatureof up to 60°C, whereby the corresponding acetoacetyl-aromatic compoundsare obtained (cf. U.S. Pat. No. 2,214,117, and R. R. Estes and A.Tockman "Transactions of the Kentucky Academy of Science," 13, page 265(1952)). In all relevant examples exclusively liquid benzene derivativesare used in a high excess as starting material, and simultaneously theyhave the function of a solvent in order that the mixtures can bestirred. The 1-arylbutane-1.3-diones obtained mostly form with thealuminum chloride, of which 2 mols must be used for each mol ofdiketene, complexes which are so stable that the desired compounds canonly be obtained therefrom by boiling them for several hours in diluteacids. In this process the used aluminum chloride is lost.

In the reaction of diketene with aromatic compounds that are solid atroom temperature, for example acenaphthene, pyrene, or2,6-dimethoxynaphthalene, solvents have to be added which do not reactwith diketene. The aforesaid literature references do not contain anydescription of corresponding experiments. In proper experiments with1,2-dichloroethane it has been found that with acenaphthene the yield isdrastically reduced and resinifications do occur and that the aluminumchloride-butanedione complexes with pyrene have a high stability. If,however, the diketene is transformed into acetoacetyl fluoride which isthen reacted with toluene in the presence of aluminum chloride inchloroform, a yield of 6.5 % only of 1-tolyl-butane-1,3-dione isobtained, calculated on the diketene (cf. G. A. Olah and S. J. Kuhn,J.Org. Chem. 26, page 225 (1961)).

The present invention provides a process for the manufacture of a seriesof aromatic 1,3-diketones in good to very good yields by reactingacetoacetyl fluoride optionally carrying in γ-position up to 3 identicalor different halogen atoms selected from the group consisting offluorine, chlorine and bromine with solid or liquid aromatic compoundsin hydrofluoric acid of at least 90 % strength, at a temperature of fromabout -40°C to +50°C, preferably about -30°C to +20°C. The optimumtemperature range slightly varies and depends on the constitution of thecompounds used. With compounds having free peri-positions, such asacenaphthene or pyrene, which may form a ring (cf. DOS 2,209,692,2,262,857 and 2,262,858) the temperature should be in the range of fromabout -40° to -10°C, preferably -30° to -20°C, whereas compounds withoutfree peri-potions are advantageously reacted at a temperature of about-30° to +20°C, preferably about - 20° to +20°C. When operating withinthe aforesaid temperature range the reaction can be carried out withoutusing special pressure resistant vessels. The vessels used arepreferably made from polyethylene, polypropylene or polyvinyl chloride,or from metal, especially steel.

Owing to the fact that in the reaction no water is formed thehydrofluoric acid used can be substantially recovered by distillation.The same applies to the portion of unreacted aromatic compounds.

The reaction pressure largely corresponds to the inherent pressure ofhydrofluoric acid which should have a minimum content of hydrogenfluoride of approximately 90 % by weight, preferably 95 to 100 % andmore preferably about 98 to 100 % by weight.

Depending on the reaction temperature the reaction time is in the rangeof from half an hour to several hours, i.e. at a reaction temperaturebelow zero degree centigrade about 6 to 24 hours, at room temperatureabout 2 to 12 hours and at about 50°C, 30 to 120 minutes.

The process of the invention can be carried out, for example, in amanner such that the aromatic compound and the acetoacetyl fluoride aredissolved in hydrofluoric acid in approximately molar proportion at atemperature expediently below 0°C, preferably about -30°C and thereaction mixture is heated to the desired reaction temperature,preferably with stirring.

It is possible to use an excess of acetoacetyl fluoride although this ishardly necessary. However, for a better utilization of the fluoride thearomatic compound may be used in an excess (about 1 to 5 mols). Thearomatic compound does not undergo secondary reactions so that theunreacted portion thereof can be recovered by known methods and usedagain in the reaction.

The hydrofluoric acid is used in an amount of from about 1 to 20 partsby weight for 1 part of aromatic compound, preferably about 3 to 10parts by weight. The reactants can be added in any order of succession,preferably one or both may be added in continuous manner. Alternatively,the whole process can be carried out continuously in simple manner byfeeding all three components uniformly to a reaction vessel or tube.Instead of acetoacetyl fluoride the analogous chloride or bromide may beused which reacts with the hydrofluoric acid to the fluoride.

The aforesaid acetoacetyl halides may be substituted in γ-position by upto 3 halogen atoms, preferably chlorine, bromine and/or fluorine. Theacetoacetyl halides substituted in γ-position by halogen atoms can beprepared by known methods, for example as described in Houben-Weyl"Methoden der Organischen Chemie", volume 7/4, page 203, published by G.Thieme, Stuttgart (1968). Particularly suitable γ-halogen-substitutedaceto-acetyl halides are γ-trifluoro-acetoacetyl fluoride,γ-trichloro-acetoacetyl chloride, ClF₂ CCOCH₂ COCl, Cl₂ FCCOCH₂ COCl,γ-mono-chloro-acetoacetyl chloride, γ-mono-bromo-acetoacetyl bromide, orγ-dichloro-acetoacetyl chloride.

The compounds may additionally carry halogen atoms in α-position,although this is less preferable.

In a preferred variant of the process of the invention the unsubstitutedacetoacetyl fluoride is produced in situ by adding diketene tohydrofluoric acid in excess (acetoacetyl fluoride from molar amounts ofdiketene and hydrogen fluoride cf. G. A. Olah and S. J. Kuhn,J.Org.Chem. 26, page 225 (1961)) in the presence or absence of thearomatic compound, preferably at about -40° to 0°C and then reacting atthe required temperature. In this mode of preparation of the acetoacetylfluoride the excess of hydrofluoric acid is suitably so high that afterthe consumption of the acid to form the fluoride the amounts necessaryfor the reaction with the aromatic compound are still available.

When the reaction is terminated the hydrofluoric acid is suitablydistilled off at atmospheric pressure and the residue is worked up bydistillation. If the aromatic component contains free peri-positions,the hydrofluoric acid is distilled off under reduced pressure and at atemperature of the still of about -30°C to -40°C or below in order toavoid ring formation. The residue is worked up in known manner byrecrystallization, column chromatography, or extraction of the desiredcompound with bases. Alternatively, the hydrofluoric acid solutionobtained when the reaction is terminated can be introduced into water,whereupon the reaction products are filtered off with suction orextracted with halohydrocarbons.

Suitable aromatic compounds to be used in the process of the inventionare, in principle, all condensed aromatics substituted or not at thering system, for example naphthalene and its derivatives, also in thelarger sense as obtained by substitution or condensation at thenaphthalene ring and containing from 10 to 20 carbon atoms, preferablyfrom 10 to 14 carbon atoms, such as the various alkyl oralkoxy-naphthalenes obtained by one- to three-fold, preferably one- totwo-fold substitution of the naphthalene ring by alkyl and/or alkoxygroups having from 1 to 4, preferably 1 or 2 carbon atoms,advantageously the various methyl- and methoxy- naphthalenes. There arenamed by way of example 1-methyl-, 2-methyl-, 1-ethyl-, 2-ethyl-,2,6-dimethyl-, 1,2,6-trimethyl-, 1-methoxy-, 2-methoxy-, 1-ethoxy-,2-ethoxy-, 1,3-dimethoxy-, 1,6-diethoxy-, 1,8-dimethoxy-, 2,3-diethoxy-,1,2,3-trimethoxy-, and 1,3,6-tributoxy-naphthalene.

Naphthalene derivatives with rings added by condensation which can beused in the process of the invention are, for example, anthracene,perylene, naphthacene or pyrene, as well as the correspondingmono-alkyl- or -alkoxy-compounds and corresponding polyalkylated orpolyalkoxylated compounds.

Besides the aforesaid compounds, which still contain free peri-positionsand are reacted in a low temperature range, substitution products ofnaphthalene in which the peri-position is blocked by a substituent mayalso be used, for example 1,4-dimethoxy- and 1,4-dimethyl-naphthalene.

Further suitable starting compounds are benzene derivatives of theformula ##SPC1##

in which R₁, R₂, and R₃, independent of one another, represent hydrogen,C₁ - C₁₂, preferably C₁ - C₆ and more preferably C₁ - C₄ -alkyl, alkoxyor alkylthio radicals, one of the radicals optionally being asubstituted phenyloxy or phenylthio radical, or halogen, preferablyfluorine, chlorine or bromine. Suitable radicals are, for example CH₃,C₂ H₅, C₃ H₇, C₄ H₉, C₆ H₁₃, OC₂ H₅, OC₃ H₇, OC₄ H₉, S--CH₃, SC₂ H₅, SC₃H₇, SC₄ H₉, O--C₆ H₅, O--CH₂ --C₆ H₅ and SC₆ H₅. In the case of one ofthe radicals R₁, R₂, or R₃ being halogen, those benzene derivatives arepreferred in which at least one of the remaining radicals is alkyl,alkoxy, or alkylthio.

Still further aromatic compounds can be used in which two of theradicals R₁, R₂, R₃ are linked to a ring or in which benzenederivatives, as specified above, are constituents of 5 or 6 memberedheterocyclic rings, for example dibenzofurane or dibenzo-p-dioxan orcompounds of the formula ##SPC2##

in which X is oxygen, sulfur or (CH₂)_(n), n being 1 to 4. Compoundshaving two benzene rings, for example diphenyl ether and thesubstitution products thereof as specified above may be reacted twice.Further suitable starting compounds are thiophene and the mono-alkyl,dialkyl and benzo derivatives thereof.

When a substance is used which reacts with diketene with difficulty onlyor not at all, it may be advantageous to add a molar amount of a furthersubstance having similar properties but being more reactive with regardto diketene. In this manner the reaction with the inactive substance canbe induced. For example, by reacting a mixture of 1 mol ofdodecyl-benzene and 1 mol of tetrahydronaphthalene with 2 mols ofdiketene in hydrochloric acid a yield of 40 % ofacetoacetyl-dodecyl-benzene can be obtained which would be hardlypossible without the addition of tetrahydronaphthalene.

Acetoacetyl-dodecyl-benzene and the compounds of the formula ##SPC3##

in which R' and R", independent of each other, are hydrogen or alkyl andthe sum of carbon atoms in the radicals R' and R" is in the range offrom 6 to 12 and Y represents hydrogen and/or fluorine, chlorine, orbromine are novel. Further novel compounds which can be prepared by theprocess of the invention, and which are of interest, aretetrahydronaphthalene acetoacetylized in α- or β-position at thearomatic ring and the acetoacetylized isomeric diethyl-benzenes.

The compounds obtained by the process of the invention can be used asintermediate and final products, for example for the formation of metalcomplexes, as metal extracting agents, as dyestuff intermediates, asmonomers for plastic materials, as intermediates for the production ofplant protection agents and pharmaceuticals, and as dissolvingintermediaries or solvents.

1-Aryl-butane-1,3-diones which can be prepared by the process of theinvention are, for example, 1-acetoacetyl-2,6-dimethoxy-naphthalene,4-acetoacetyl-diphenyl-sulfide, 2-chloro- and2-bromo-4-acetoacetyl-anisole, 3-acetoacetyl-diphenylene oxide,2,2'-dimethoxy-4,4'-bisacetoacetyl-diphenyl ether,3-chloro-6-acetoacetyl-pyrene, 1-methyl-4-acetoacetyl-naphthalene,3-acetoacetyl-pyrene and 1-methoxy-4-acetoacetylnaphthalene.

The following examples illustrate the invention.

EXAMPLE 1

165.6 g (1.2 mols) of 1,2-dimethoxybenzene in 600 ml of anhydroushydrofluoric acid were introduced, while stirring at -20°C, into a 1liter polyethylene vessel and 108 ml (1.4 mols) of diketene were droppedin while further cooling. Stirring was continued for 4 hours whilecooling with ice, the reaction mixture heated for 3 hours at roomtemperature and the hydrofluoric acid distilled off. The residue waswashed to remove the acid and subjected to vacuum distillation, wherebythe 1,2-dimethoxy-4-acetoacetyl-benzene passed over at a boiling pointof 132°C under 0.05 torr (mm. Hg), which solidified in the form ofcolorless crystals.

Yield: 219 g, i.e. 82.3 % of the theory, calculated on the amount of1,2-dimethoxy-benzene used.

EXAMPLE 2

150 ml of anhydrous hydrofluoric acid were introduced at -30°C into asteel vessel, 18 ml (0.23 mol) of diketene and then 21.2 g (0.2 mol) ofm-xylene were added dropwise. The reaction mixture was allowed to warmup to room temperature. After 7 hours the hydrofluoric acid wasdistilled off while thoroughly stirring. The residue was washed until itwas free from acid and by distillation were obtained 35 g (92 %,calculated on m-xylene) of a mixture boiling at 99° - 104°C andconsisting according to the gas chromatogram of 96.9 % of1,3-dimethyl-4-acetoacetyl-benzene and 2.7 % of1,3-dimethyl-2-acetoacetyl-benzene.

EXAMPLE 3

In an autoclave 27 ml (0.35 mol) of diketene were added dropwise at-30°C to 150 ml of anhydrous hydrofluoric acid and then 31.8 g (0.3 mol)of o-xylene were added. After 4 hours stirring at room temperature, themixture was heated for 30 minutes to 50°C. After distillation of thehydrofluoric acid and washing out the residual acid, 44 g (78 %,calculated on o-xylene) of a mixture passed over at 110° - 115°C under0.6 torr, which consisted of 92 % of 1,2-dimethyl-4-acetoacetyl-benzeneand 7 % of 1,2-dimethyl-6-acetoacetyl-benzene according to the gaschromatogram.

Using p-xylene 1,4-dimethyl-2-acetoacetyl-benzene distilling over at99°C under 0.7 torr was obtained in analogous manner in a yield of 67 %.

EXAMPLE 4

54 ml (0.7 mol) of diketene were added dropwise at 0°C to 72 g (0.6 mol)of mesitylene in 500 ml of anhydrous hydrofluoric acid and after 6 hoursstirring at room temperature the reaction mixture was stirred into 3 lof water. After standing overnight 115 g (94 % calculated on mesitylene)of colorless crystals of acetoacetyl-mesitylene melting at 41°Cseparated, which were found to be uniform by thin layer chromatography.

EXAMPLES 5 to 21

The reaction was carried out as described in Example 2. The results aresummarized in the following table.Example starting comp- mol di- finalproduct yield melting pointNo. ound (A) ketene (%) °C or per mol boilingpoint of A°C/torr__________________________________________________________________________52-chloroanisole 1 4-acetoacetyl- 79 129 2-chloroanisole6 2-bromoanisole1 4-acetoacetyl- 63 123 2-bromoanisole7 diphenyleneoxide 13-acetoacetyl- 74 125 diphenylene oxide8 diphenyl ether 1 4-acetoacetyl-59 80 diphenyl ether9 diphenyl ether 2 4-4'-bis-aceto- acetyl-diphenyl-19 152 ether besides 4-acetoacetyl. 39 diphenyl ether10 2,2'-dimethoxy-2 4,4'-bis-aceto- diphenyl ether acetyl-2,2'-di- 43 142 methoxy-di-phenyl ether11 diphenyl sulfide 1 4-acetoacetyl- diphenyl sulfide 397512 4-methylanisole 1 2-acetoacetyl- 81 115/0.1 torr 4-methylanisole13anisole 1 4-acetoacetyl- 71 54 anisole 2-acetoacetyl anisole 12 3614toluene 1 4-acetoacetyl- 80 toluene 2-acetoacetyl- 7 110/0.9 torrtoluene15 p-Xylene 1 1,4-dimethyl- 2-acetoacetyl- 69 99/0.7 torrbenzene16 m-hexyltoluene 1 acetoacetyl-⁺.sup.) 63 135-145/ hexyltoluene1.5 torr17 tetrahydro- acetoacetyl-⁺.sup.) 160-165/ naphthalene 1tetrahydro- 79 1.5 torr naphthalene18 di-isopropyl- acetoacetyl-⁺.sup.)benzene+) 1 di-isopropyl- 61 140/1.5 torr benzene19 diethyl-benzene +) 1acetoacetyl-⁺.sup.) 120-138/ di-ethyl- 59 0.6 torr benzene20 thiophene 12-acetoacetyl- 67 32 thiophene21 cumene 1 4-acetoacetyl- 75 120/2 torrcumene__________________________________________________________________________

EXAMPLE 22

33.6 g (0.4 mol) of diketene were added drop by drop, while stirring at-30°C, to 37.6 g (0.2 mol) of 2,6-dimethoxynaphthalene in 200 ml ofanhydrous hydrofluoric acid and the mixture was stirred for another 8hours at said temperature. The hydrogen fluoride was distilled off underreduced pressure at a temperature of the still of -30°C and the residuewashed until it was free from acid. After sublimation of unreactedstarting product (11 g = 71 % conversion) colorless crystals of1-acetoacetyl-2,6-dimethoxynaphthalene melting at 88°C were obtained bycolumn chromatography (silica gel, 0.065 - 0.2 mm, CH₂ Cl₂) in an amountof 35 g (90 % calculated on 2,6-dimethoxynaphthalene).

EXAMPLE 23

42 g (0.5 mol) of diketene were added dropwise to 77 g of acenaphthene(0.5 mole) in 300 ml of anhydrous hydrofluoric acid at -30°C whilestirring. The temperature was maintained for 9 hours. The hydrofluoricacid was distilled off under reduced pressure at a temperature of thestill of -30°C, the residue was washed until it was free from acid anddistilled under reduced pressure. 10 g of unreacted acenaphthene wererecovered (87 % conversion). At a transition temperature of 150° - 155°Cunder 0.4 torr 85 g (82 % of theory) of slightly yellowish5-acetoacetyl-acenaphthene melting at 59°C were then obtained.

EXAMPLE 24

42 g (0.5 mol) of diketene were added dropwise at -40°C to 79 g (0.5mol) of 2-methoxy-naphthalene in 300 ml of anhydrous hydrofluoric acid,stirring was continued for 7 hours at -25° to -35°C and the reactionmixture was stirred into 3 1 of water. After extraction with methylenechloride, drying and eliminating the solvent, the residue was distilled.First 12 g of methoxy-naphthalene were recovered at 95°C/0.5 torr (84.5% conversion) and then 90 g (86.5 %) of1-acetoacetyl-2-methoxynaphthalene melting at 77°C (recrystallized fromethanol) passed over at 163°C/0.8 torr.

EXAMPLES 25 and 26

The reaction was carried out as described in Example 24. The result issummarized in the following tableExample starting comp- mol di- finalproduct yield melting p.No. ound (A) ketene (%) °C or per mol boiling p.of A°C/torr__________________________________________________________________________251-methoxy- 1 1-methoxy-4- naphthalene acetoacetyl- 77 178/0.3naphthalene torr26 1-methyl- naphthalene 1 1-methyl-4- acetoacetyl- 89145/0.3 naphthalenetorr__________________________________________________________________________

EXAMPLE 27

100.8 g (1.2 mols) of diketene were dropped at -20°C into 500 ml ofanhydrous hydrofluoric acid and at the same temperature 242.4 g (1.2mols) of pyrene were added in portions, whereupon the mixture wasstirred for 16 hours at -15 to -10°C. After distillation of thehydrofluoric acid at a temperature of the still of -15° C at reducedpressure, the residue was taken up in methylene chloride, washed withwater and dried over sodium sulfate. After elimination of the solvent,307 g of yellow crystals of 3-acetoacetyl-pyrene were obtained,corresponding to a yield of 89 %.

After recrystallization from cyclohexane, the yellow crystals obtainedmelted at 86° - 88°C.

EXAMPLE 28

In the manner described in Example 27 3-chloro-6-acetoacetyl-pyrenemelting at 105°C was obtained in a 71 % yield from 3-chloropyrene.

EXAMPLE 29

The following compounds

2-methyl-1-acetoacetyl-naphthalene

2,7-dimethoxy-1-acetoacetyl-naphthalene and

3-acetoacetyl-perylene

were prepared in the manner described in Example 24.

Furthermore

1,4-dimethyl-5-acetoacetyl-naphthalene and

1,4-dimethoxy-5-acetoacetyl-naphthalene

were prepared as described in Example 2

EXAMPLE 30

100.8 g (1.2 mols) of diketene were added dropwise at -30°C to 0.5 1 ofanhydrous hydrofluoric acid and a mixture of 0.6 mol oftetrahydronaphthalene and 0.6 mol of commercial grade dodecyl-benzenewere dropped in. After stirring for 12 hours at room temperature, thereaction mixture was stirred into 3 1 of icewater. After extraction withmethylene chloride, wahing with water to remove the acid from theorganic phase and distillation of the methylene chloride, distillationof the reaction yielded 86 % of acetoacetyl-tetrahydronaphthaleneboiling at 135°C under 0.5 torr and 77 g 40% ofacetoacetyl-dodecyl-benzene boiling at 160°C under 0.5 torr as found bygas chromatographic determination of the fractions.

EXAMPLE 31

Crude γ-trichloro-acetoacetyl chloride, prepared from 0.5 mol each oftrichloroacetyl chloride and ketene (cf. Houben-Weyl, loc.cit) wascarefully freed from the solvent and dropped at -20°C while stirringinto 0.5 1 of hydrofluoric acid. Next, 0.5 mol of m-xylene was added,the reaction mixture was stirred for 10 hours at room temperature,poured into icewater and extracted with methylene chloride.

After distillation 79 g of light yellow, liquid1-γ-trichloroacetoacetyl-2,4-dimethyl-benzene were obtained which had astrength of 94.5 % according to gas chromatography. Theoretical yieldover two stages 50.5 %, boiling point 166°C under 2 - 3 torr.

EXAMPLE 32

The reaction was carried out analogous to Example 31 withγ-trifluoroacetoacetyl-chloride and mesitylene in hydrofluoric acid.1-γ-trifluoroacetoacetyl-2,4,6-trimethylbenzene was obtained as a lightyellow liquid boiling at 80° - 82°C under 0.8 torr.

EXAMPLE 33

0.5 mol of γ-chloroacetoacetyl chloride (as crude product after removalof solvent, cf. Houben-Weyl loc.cit, pages 252/2) and 0.5 mol of2-anisyl-chloroacetic acid ester were introduced at -10°C into 0.5 1 ofhydrofluoric acid and stirring was continued for 8 hours at 15°C.

By pouring the reaction mixture into icewater, extraction and columnchromatography (silica gel 0.05 - 0.2 mm, CH₂ Cl₂) colorless crystals of3-γ-chloroacetoacetyl-6-methyl-chloroacetic acid phenyl ester melting at107°C were obtained.

EXAMPLE 34

When toluene was used 4-γ-chloroacetoacetyl-toluene was obtained inanalogous manner as a light brown, readily decomposable liquid having arefractive index n_(D) ²³ of 1.6008 in a yield of 30 % (over two stages,calculated on the diketene used.

EXAMPLE 35

When crude γ-bromoacetoacetyl bromide (literature cf. Example 33) andmesitylene were reacted in analogous manner, γ-bromoacetoacetylmesitylene was obtained as a brown readily decomposable liquid which wascharacterized by nuclear magnetic resonance spectrum as follows:

    NMR (CDCl.sub.3, TMS, δ)                                                               2.32 ppm    3 × CH.sub.3                                                                       (s)                                                    3.90 ppm                                                       CH.sub.2 Cl    (s)                                                                           5.90 ppm                                                       CH =           (s)                                                                           6.84 ppm    2 arom. H  (s)                                                    14.00 ppm   enol-H     (s)                                 

EXAMPLE 36

When toluene was used in a manner analogous to that of the precedingexample and the reaction mixture was worked up in a chromatographiccolumn 1-p-tolyl-4-bromo-butane-dione-1,3 was obtained in the form oflight pink crystals melting at 52°C

What is claimed is:
 1. A compound of the formula ##SPC4##wherein R' andR" each is hydrogen or alkyl and R' and R" together contain 6 to 12carbon atoms, and each Y is hydrogen, fluorine, chlorine or bromine. 2.α-and β-acetoacetyl-tetrahydronaphthalene of the formula ##SPC5## 3.Isomeric acetoacetyl-dialkyl benzenes of the formula ##SPC6##